A Phase 3, Randomized, Double blind, Placebo controlled, Multicenter Study of Bendamustine and Rituximab (BR) alone Versus in Combination with Acalabrutinib (ACP 196) in Subjects with Previously Untreated Mantle Cell Lymphoma

Phase 1

• Conditions: Mantle Cell Lymphoma; MedDRA version: 20.0Level: HLTClassification code 10026798Term: Mantle cell lymphomasSystem Organ Class: 100000004943; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-005220-26-FR
• Lead Sponsor: Acerta Pharma BV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-08-10
• Last Update Posted: 3 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 546

Inclusion Criteria

1. Men and women, = 65 years of age.
2. Pathologically confirmed MCL, with documentation of monoclonal CD20+ B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1.
3. MCL requiring treatment and for which no prior systemic anticancer therapies have been received.
4. Presence of radiologically measurable lymphadenopathy or extranodal lymphoid malignancy (as defined by Lugano Classification for NHL).
5. ECOG performance status of = 2.
6. Men who are sexually active and can beget children must agree to use highly effective forms of contraception during the study and for 90 days after the last dose of acalabrutinib, 6 months after the last dose of bendamustine, or 12 months after the last dose of rituximab, whichever is longest. Highly effective forms of contraception are defined in Section 9.2.2.
7. Men must agree to refrain from sperm donation during the study and for 90 days after the last dose of acalabrutinib, 6 months after the last dose of bendamustine, or 12 months after the last dose of rituximab, whichever is longest.
8. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
9. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 546

Exclusion Criteria

1.History of prior malignancy except for the following:
a.Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening and felt to be at low risk for recurrence by treating physician. Note: Provided they meet other eligibility criteria, subjects who are receiving hormonal therapy alone are allowed to enroll on study.
b.Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanomatous skin cancer.
c.Adequately treated carcinoma in situ without current evidence of disease.
2.Subjects for whom the goal of therapy is tumor debulking before stem cell transplant.
3.Any history of CNS lymphoma or leptomeningeal disease.
4.Uncontrolled AIHA or ITP.
5.Major surgical procedure within 28 days before first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
6.Significant cardiovascular disease such as uncontrolled or untreated symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of first dose of study drug, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or QTc > 480 msec (calculated using Friderica’s formula: QT/RR0.33) at screening. Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll on study.
7.ANC < 1.0 x 109/L or platelet count < 75 x 109/L; for subjects with disease involvement in the bone marrow, ANC < 0.75 x 109/L or platelet count < 50 x 109/L. Subjects will only be considered eligible if peripheral blood counts can be maintained independent of growth factors or transfusions during the screening period.
8.Total bilirubin > 1.5 x ULN; or AST or ALT > 2.5 x ULN.
9.Estimated creatinine clearance of < 50 mL/min, calculated using the formula of Cockcroft and Gault [(140-Age)•Mass (kg)/(72•creatinine mg/dL)•multiply by 0.85 if female].
10.Prothrombin time/INR or aPTT (in the absence of a Lupus anticoagulant) > 2.0 x ULN. Exception: Subjects receiving warfarin are excluded; however, those receiving other anticoagulant therapy who have a higher INR/aPTT may be permitted to enroll to this study after discussion with the medical monitor.
11.Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
12.Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), or intravenous anti infective treatment within 2 weeks before first dose of study drug.
13.Known history of infection with HIV.
14.Ongoing immunosuppressive therapy, including systemic (eg, IV or oral) corticosteroids within 2 weeks before the first dose of study drug. Note: Subjects may use topical or inhaled corticosteroids or low dose steroids as therapy for comorbid conditions. During study participation, subjects may also receive systemic (eg, IV or oral) corticosteroids as needed for treatment emergent comorbid conditions.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified